Mitochondrial biogenesis requires the joint efforts of two distinct protein synthesizing systems each containing its own unique set of genetic information. Recent evidence indicates that these two systems, the mitochondrial and the nucleocytoplasmic, exhibit some degree of interdependence. The mechanism of this interdependence is rapidly becoming one of the key problems of mitochondrial biogenesis. We wish to outline a novel experimental approach that should greatly facilitate the elucidation of these control interactions between the two protein synthesizing systems and, at the same time, should also advance our understanding of organelle assembly and the physical basis of extrachromosomal genetics. Current evidence suggests that the synthesis of most cellular components during the cell cycle consists of a series of highly ordered and reproducible temporal events. This orderly sequence has been likened to the organized series of morphogenetic and biochemical events known to occur during the developmental scheme in multicellular organisms. Just as perturbations in the normal developmental sequence have established clearly discernible control interactions in which certain events are necessary prerequsites for other events that follow, we intend to employ a similar approach to elucidate control interactions necessary for mitochondrial biogenesis. The normal sequence of formation of several uniquely mitochondrial parameters including mitochondrial DNA and mitochondrial inner membrane polypeptides will be defined during the cell cycle in the yeast, Saccharomyces cerevisiae. The effects of lesions in either protein synthesizing system will be examined in both the "target" system and in the "other" system. These effects will be interpreted with respect to control interactions present between the two systems.